The metal binding properties of chicken ovotransferrin and human serum tranferrin will be characterized. The initial studies will be on chicken ovotransferrin because of its relative inexpensiveness. These studies will be repeated and extended with human serum transferrin. In particular, the protein side chains of human serum transferrin involved in iron binding will be characterized by the use of chemical modification as a major tool. In addition, the anion binding sites in the protein will be studied by similar procedures. With the anion binding site, one of the approaches will include an attempt of affinity labeling by using anions with potentially reactive groups capable of forming derivatives of protein side chains in the vicinity of the anion binding site. Also, an extension of this approach to include photo-affinity labeling will be attempted. The studies will then be extended to the use of this information, as well as many of the derivatives, to the transfer of iron from iron serum transferrin into the developing reticulocyte. The chemical modifications will include those directed particularly at tyrosines and histidines. But other groups will also be considered because of their possible presence in the vicinity of the binding site and, in particular, because of the possibility that they may interact with the anions necessary for the formation of the ternary complex between the transferrin, the iron, and the anion. Consideraton will also be given to the synthesis of derivatives of transferrin which would be useful in clinical research as well as in therapeusis.